Can amyloidosis involve the lungs?

Pulmonary Involvement in Amyloidosis

Yes, amyloidosis can definitively involve the lungs through multiple distinct patterns, including diffuse alveolar-septal deposition, tracheobronchial infiltration, nodular parenchymal disease, cystic lung disease, and pleural involvement. 1, 2

Patterns of Pulmonary Amyloidosis

Pulmonary amyloidosis manifests in both localized and systemic forms, with fundamentally different clinical implications and treatment approaches 1, 3:

Localized Pulmonary Amyloidosis

Localized tracheobronchial amyloidosis represents a distinct entity that does not progress to systemic disease and results from local synthesis of amyloid protein rather than distant deposition. 1 This form typically presents with:

• Tracheobronchial involvement causing cough, wheezing (frequently misdiagnosed as asthma), and hemoptysis, with average diagnosis age around 55 years 1, 4
• Bronchoscopic findings showing diffuse submucosal infiltration appearing nodular, tumor-like, or polypoid 1, 4
• Nodular parenchymal disease presenting as single or multiple lung nodules on imaging 2, 5
• Cystic lung disease as a rare manifestation 6

Systemic Amyloidosis with Pulmonary Involvement

Systemic amyloidosis, particularly AL (light chain) amyloidosis, commonly affects the lungs alongside other organs, most critically the heart and kidneys. 3, 2 Pulmonary manifestations include:

• Diffuse alveolar-septal amyloidosis as the most common type, typically associated with systemic AL amyloidosis, which can impair gas exchange when interstitial involvement is extensive 2, 6
• Pleural involvement with effusions and pleural thickening occurring frequently in systemic disease 5, 6
• Mediastinal and hilar lymphadenopathy as additional manifestations 5
• Pulmonary hypertension reported in some cases 2

Critical Diagnostic Approach

When pulmonary amyloidosis is suspected, distinguishing localized from systemic disease is mandatory, as systemic disease requires aggressive systemic therapy and carries significantly higher mortality. 3, 4

Essential Workup Steps:

1. Tissue diagnosis with Congo red staining showing apple-green birefringence under polarized light is pathognomonic and mandatory 4

2. Amyloid protein typing using mass spectrometry (88% sensitivity, 96% specificity) is critical because treatment differs fundamentally between AL and ATTR amyloidosis 4

3. All cases require serum and urine immunofixation plus serum free light chain assay to exclude systemic AL amyloidosis, even when disease appears localized 3, 4

4. Cardiac evaluation with NT-proBNP (>332 ng/L has >99% sensitivity for cardiac involvement) and troponin T is essential, as cardiac involvement is the most important prognostic factor 3, 4

5. Renal assessment with 24-hour urine protein and eGFR should be performed 4

Imaging Considerations:

Chest X-rays are insensitive for detecting tracheobronchial amyloidosis; CT is superior, showing irregular luminal narrowing, airway wall thickening with calcifications, and soft tissue shadows. 5 However, imaging alone is insufficient—tissue diagnosis is mandatory. 4

Treatment Implications

Treatment strategy depends entirely on whether disease is localized or systemic:

Localized Disease:

• Bronchoscopic debulking and laser ablation for tracheobronchial disease, though recurrence is common 1
• External beam radiation therapy as an alternative 2
• Close monitoring for asymptomatic cases 2

Systemic Disease:

• Systemic therapy targeting underlying protein production is required, including chemotherapy, daratumumab, proteasome inhibitors, or autologous stem cell transplantation for AL amyloidosis 3
• Treatment of diffuse alveolar-septal amyloidosis follows the treatment protocol for underlying systemic amyloidosis 2
• Collaboration between pulmonologists, cardiologists, and hematologists is essential 3

Prognostic Considerations

Systemic amyloidosis with cardiac involvement has dramatically worse outcomes, with median survival dropping from 13 months to just 4 months when heart failure symptoms develop in AL amyloidosis. 3 Even when amyloidosis appears confined to the lungs, subclinical involvement of other organs may be present but not yet detectable, necessitating comprehensive evaluation. 3

The long-term prognosis of pulmonary amyloidosis depends primarily on the type of lung involvement and the function of other organs, particularly the heart. 2

Common Pitfalls to Avoid

• Never rely on imaging alone without tissue confirmation 4
• Never assume localized disease without comprehensive systemic workup including cardiac biomarkers and serum/urine immunofixation 3, 4
• Never proceed with treatment without amyloid protein typing, as AL and ATTR amyloidosis require fundamentally different therapeutic approaches 4
• Never overlook cardiac involvement assessment, as it is the most critical prognostic determinant 3